In Vitro inhibition of melanoma cell growth and viability by progesterone - an off-target protective function?

Document Type

Article

Publication Title

Progesterone: Functions, Uses and Research Insights

Abstract

Progesterone is a female sex hormone, which increases and decreases during menstrual cycle. Progesterone has been associated with female reproductive functions especially pregnancy and breast, ovary and endometrial cancers. This chapter highlights an off-target effect of progesterone on skin cancer melanoma. Melanoma is a fatal form of skin cancer, which is on the rise. There is an increased mortality rate in males than in females in melanoma, indicating a sex difference. Clinical studies showed that menstruating females were better protected in melanoma than post-menopausal women and men of any age, suggesting the involvement of sex steroid hormones in the protection. But these clinical studies did not correlate with sex steroids status of females and did not show any direct effect of sex steroids on melanoma cells. In this context, our published work indicated a direct effect of progesterone on melanoma cell growth in-vitro. Others also observed in-vitro inhibition of melanoma cell growth by progesterone at different contexts, but did not relate it to protective function in females. Our initial in-vitro study with various sex steroids indicated that progesterone, a female sex hormone significantly inhibiting mouse melanoma (B16F10) cell growth. Results suggested that this effect was not a toxic, spurious or non-specific effect on mouse melanoma cells. In addition, this effect was not mediated through progesterone receptor in mouse melanoma cells. Based on mouse melanoma cell line study, research work was extended to human melanoma (BLM) cell line. Progesterone inhibited human melanoma cell growth also significantly and the mechanism of inhibition of cell growth was due to autophagy. This effect was also not mediated through progesterone receptor. This in-vitro study not only indicated an off-target effect of progesterone, but also suggested progesterone as a possible sex steroid hormone protecting menstruating females in melanoma, as underscored by the clinical studies.

First Page

57

Last Page

67

Publication Date

1-1-2016

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